title: Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice.
abstract: Fat tissue plays an important role in the regulation of inflammatory processes. Increased visceral fat has been associated with a higher production of cytokines that triggers a low-grade inflammatory response, which eventually may contribute to the development of insulin resistance. In the present study, we investigated whether glycine, an amino acid that represses the expression in vitro of pro-inflammatory cytokines in Kupffer and 3T3-L1 cells, can affect in vivo cytokine production in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Our data demonstrate that glycine treatment in lean mice suppressed TNF-alpha transcriptional expression in fat tissue, and serum protein levels of IL-6 were suppressed, while adiponectin levels were increased. In MSG/Ob mice, glycine suppressed TNF-alpha and IL-6 gene expression in fat tissue and significantly reduced protein levels of IL-6, resistin and leptin. To determine the role of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the modulation of this inflammatory response evoked by glycine, we examined its expression levels in fat tissue. Glycine clearly increased PPAR-gamma expression in lean mice but not in MSG/Ob mice. Finally, to identify alterations in glucose metabolism by glycine, we also examined insulin levels and other biochemical parameters during an oral glucose tolerance test. Glycine significantly reduced glucose tolerance and raised insulin levels in lean but not in obese mice. In conclusion, our findings suggest that glycine suppresses the pro-inflammatory cytokines production and increases adiponectin secretion in vivo through the activation of PPAR-gamma. Glycine might prevent insulin resistance and associated inflammatory diseases.
authors.affiliation: Laboratorio de Farmacologia, Departamento de Ciencias de la Salud, Div. de Ciencias Biologicas y de la Salud, Universidad Autonoma Metropolitana Unidad Iztapalapa, Mexico, D.F. Mexico. aaasj2@prodigy.net.mx
authors.forename: F J
authors.initials: FJ
authors.lastname: Alarcon-Aguilar
authors.forename: Julio
authors.initials: J
authors.lastname: Almanza-Perez
authors.forename: Gerardo
authors.initials: G
authors.lastname: Blancas
authors.forename: Selene
authors.initials: S
authors.lastname: Angeles
authors.forename: Rebeca
authors.initials: R
authors.lastname: Garcia-Macedo
authors.forename: Ruben
authors.initials: R
authors.lastname: Roman
authors.forename: Miguel
authors.initials: M
authors.lastname: Cruz
mesh_terms: D016475:3T3 Cells; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D005998:Glycine / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000503:physiopathology*; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D052243:Resistin / Q000378:metabolism; D012970:Sodium Glutamate / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D052242:Adiponectin; D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D047495:PPAR gamma; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose; D005998:Glycine; D012970:Sodium Glutamate